The Keynote lecture on Day 3 was from Hans Clevers, who is director of, and runs a lab at, the Hubrecht Institute in Utrecht and is also President of the Royal Netherlands Academy of Arts and Sciences. Clevers gave an amazing presentation of his lab’s work on intestinal stem cells that was accompanied by movie-quality animations that really helped visualize the significance of his results. The intestinal epithelium has very interesting morphology: we all know about villi and their importance in digestion but in between the villi are ‘crypts’, narrow tunnels at the bottom of which lie the intestine’s stem cells. Each crypt makes 200 cells/day so this is a very active stem cell compartment. It has to be because the cells of this epithelium must be replaced every 4-5 days. Defining the stem cell population in the crypt has been challenging and the subject of much controversy. Clevers’ lab has made great strides in this area using sophisticated genetic engineering techniques that allow them to mark and manipulate single cells in the mouse intestine (for a great review on lineage tracing in epithelia, click here). They identified a population of columnar epithelial cells at the bottom of the crypt, positive for the marker Lgr5 (see figure), that give rise to all the cell types of the intestine. The surrounding Paneth cells serve as the niche for these stem cells. They isolated these Lgr5-positive cells, figured out the conditions to grow them in vitro and found, amazingly, that these single cells could grow into ‘miniguts’ with the right tissue morphology. They then introduced these miniguts into mice and found that they attached only to damaged epithelia (which occurs for example with ulcers) and sealed the lesion, without any occurrence of adenomas. These miniguts have great therapeutic potential; Clevers showed that they can grow miniguts from intestinal stem cells isolated through patient biopsies and test the efficacy of drugs on this pseudotissue. For example, they have used the miniguts to monitor CFTR channel function and test cystic fibrosis drugs. I found this to be a very inspiring talk: this lab came to this field through a long standing interest in Wnt signaling and now are actively exploring the therapeutic potential of their findings. It really was a tour-de-force example of how basic cell biology can lead to more clinical applications.